title: IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma.
abstract: IL-17, which exerts strong pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. However, the characteristics of IL-17-producing cells, the relevance of IL-17 to clinical parameters and its function in the development and progression of colorectal carcinoma still remain to be explored. In the present study, we first found the levels of IL-17 producing cells were significantly increased in the tumor regions of samples from colorectal carcinoma patients compared with non-tumor regions. Confocal microscopic analysis showed co-staining of IL-17 with CD4 and CD68, indicating IL-17 in colorectal carcinoma was expressed by macrophage and Th17. High expression of IL-17 was associated with high microvessel density. Univariate and multivariate analysis revealed that IL-17 was an independent prognostic factor for overall survival. To explore the underlying mechanisms of IL-17 in angiogenesis, we used PCR-array to find pro-angiogenic factor in cancer cells specifically induced by IL-17, then validated VEGF as one of factors in IL-17-mediated angiogenesis with the use of quantitative RT-PCR, ELISA and VEGF immunohistochemistry. Our results propose IL-17 as a novel indicator of prognosis in the patients with colorectal carcinoma and could serve as a novel therapeutic target for colorectal carcinoma, furthermore our results indicate that IL-17 producing cells may facilitate development of colorectal carcinoma by fostering angiogenesis via promote VEGF production from cancer cells.
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Liu
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Duan
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Cheng
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Haixia
authors.initials: H
authors.lastname: Long
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Lin
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D002277:Carcinoma / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D055815:Young Adult; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018956:CD5 Antigens; D020381:Interleukin-17; D042461:Vascular Endothelial Growth Factor A; C067980:CD68 antigen, human; D000097382:CD68 Molecule